Volume 22, Number 1 January 2008 Drugs & Therapy B � U � L � L � E � T � I � N FORMULARY UPDATE PRESCRIBING The Pharmacy and Therapeutics Committee met November 20, 2007. Discontinue stress, discontinue 2 drugs were added in the Formu- lary, and 4 drugs or dosage forms stress ulcer prophylaxis were deleted. 5 drugs or dosage tress ulcers are superficial lesions should be discontinued in patients with- forms were designated nonformulary involving the mucosal layer of the out an additional indication for use (eg, and not available. Criteria for use S stomach that appear after major stressful gastrointestinal reflux disease [GERD] or were changed for 3 drugs. events.1 Critically ill patients admitted history of GI bleed). When a patient trans- to intensive care units (ICUs) are at an fers or is discharged from an ICU, there is ◆ ADDED increased risk for suffering from compli- an opportunity to discontinue SUP. Ambrisentan cations related to stress ulceration.2 As An audit of SUP use in the ICUs at (Letairis® by Gilead Sciences)* such, stress ulcer prophylaxis (SUP) is Shands at UF was recently conducted. *Restricted to patients approved for the appropriate for many critically ill patients. Thirty adult patients receiving SUP were Letairis Education and Access Program SUP is defined as any medication used followed during their hospital admis- to prevent formation of stress ulcers and sion, beginning upon admission to the Anidulafungin includes antacids, sucralfate, prostaglan- surgical intensive care unit (SICU). When (Eraxis® by Pfizer)† din analogues, histamine H2-receptor mechanical ventilation and coagulopathy †Restricted to approval by the ID antagonists, and proton-pump inhibitors were no longer present, SUP was no lon- Consult Service, Dr. Wingard, or the (PPIs). Although these therapies are con- ger considered necessary. Other reasons Antimicrobial Management Program sidered effective, there are disadvantages to continue SUP included acid suppres- associated with their use. A higher gas- sion therapy prior to admission, or a past ◆ DELETED tric pH is associated with gastric microbi- medical history of GERD or a GI bleed. Aprotinin (Trasylol® by Bayer)‡ al growth, tracheobronchial colonization, Upon transfer from the SICU, 73% of 3 patients were continued inappropriately, ® ‡ and nosocomial pneumonia. Unnecessary Caspofungin (Cancidas by Merck) use of acid suppression therapy has been 16% continued appropriately, and only Itraconazole, Intravenous associated with the development of com- 11% discontinued appropriately. A similar (Sporanox® by Ortho Biotech)‡ munity-acquired pneumonia, as well as evaluation was conducted for 30 patients community-acquired Clostridium difficile in the medical intensive care unit (MICU). Ranitidine Effervescent Tablets infections.4,5 Both studies were conducted Upon transfer from the MICU, 36% were (Zantac® Efferdose by Glaxo- in outpatients and found an association continued inappropriately and 64% con- SmithKline)‡ between the use of acid suppression tinued appropriately. SUP was discontin- ‡Nonformulary and Not Available therapy and infection.4,5 In addition, long- ued appropriately in none of the patients. term PPI use, particularly at high-doses, The evaluation also indicated that some ◆ NONFORMULARY AND has been associated with an increased patients (ie, 15% from the SICU and 5% NOT AVAILABLE risk of hip fracture (ie, osteoporosis).5 SUP from the MICU) were discharged from the Ramelteon (Rozerem® by Takeda also increases the number of medications hospital on acid suppression therapy with Pharmaceuticals) a patient receives, as well as the cost of no indication for continued use. their treatment.3 The results of this audit show that ◆ CRITERIA-FOR-USE CHANGES Several risk factors have been identi- some critically ill patients are unneces- fied for the development of stress ulcers, sarily continued on SUP upon discharge Altretamine (Hexalen® by MGI including respiratory failure, coagulopa- from the ICUs. SUP should be discontin- Pharma)§ thy, hypotension, sepsis, hepatic failure, ued upon elimination of risk factors. §Requires a Chemotherapy Order renal failure, surgery, burns, and major Appropriate use of SUP may translate Form; Nonformulary. trauma.2 A prospective, multi-center to a reduction in adverse events and Ceftriaxone (Rocephin® & generics)** cohort study conducted by Cook and healthcare expenditures. By Sarah Bush, PharmD ** colleagues identified 2 independent risk Resticted:Cannot be used in infants factors for bleeding. The strongest risk (References listed on page 4) 28 days old or less factors are mechanical ventilation for Meningococcal Polysaccharide more than 48 hours and coagulopathy, Diphtheria Toxoid Conjugate Vac- defined as a platelet count less than ◆ ® †† 3 cine (Menactra by Sanofi Pasteur) 50,000 mm , an International Normalized INSIDE THIS ISSUE ††Can be used in patients from 2–55 Ratio (INR) of greater than 1.5, or a partial thromboplastin time of greater than 2 years of age ◆ P&T 2007 times the control value.2 (continued on next page) When risk factors no longer exist, SUP Formulary update, from page 1 Anidulafungin was added in the For- significant higher rate compared with Ambrisentan was approved by the mulary as the sole representative of the either of the other treatment arms. FDA in June 2007 with a labeled indi- echinocandin antifungal agents. Caspo- This trend of higher mortality with cation for the treatment of pulmonary fungin was deleted from the Formulary aprotinin was observed throughout arterial hypertension (WHO Group 1) and designated nonformulary and not the study. Although less blood was in patients with WHO class II or III available. Micafungin (Mycamine®) re- used in the aprotinin arm compared symptoms to improve exercise capac- mains nonformulary and not available. with either of the other treatments, ity and delay clinical worsening. It is The echinocandins were originally more deaths due to hemorrhage were an alternative to bosentan (Tracleer®), reviewed in November 2006. At that observed in the aprotinin arm. The which is listed in the Formulary but time, caspofungin, micafungin, and data safety monitoring board con- restricted to patients who have been anidulafungin were deemed equiva- cluded that continued enrollment of approved for bosentan’s restricted lent. Caspofungin was selected as the patients was unlikely to change these drug distribution program. formulary agent, and micafungin and findings. Due to the risk of hepatic injury anidulafungin were designated nonfor- The FDA is currently evaluating and birth defects, ambrisentan also is mulary and not available. these results and determining what only distributed through a restricted The echinocandins were re-evalu- additional actions are needed (eg, drug distribution program (ie, the Le- ated because increased competition further modification of the product tairis Education and Access Program among these products has resulted in labeling or permanently pulling the [LEAP]). Prescribers and pharma- cost reductions. Little new evidence drug from the market). These data cists must call 866-663-LEAP (5327) has been published in the last year. from a randomized controlled trial to enroll patients. In order to stock There is a study showing equivalency are consistent with an observational ambrisentan, hospitals must sign an of micafungin at doses of 100 mg and study published approximately a year agreement that it will be dispensed 150 mg once daily with standard doses ago that also found a higher rate of only to patients who are already en- of caspofungin for the management of mortality with aprotinin. The Director rolled in the restricted drug distribu- candidemia and invasive candidiasis. In of the Office of New Drugs was quot- tion program (ie, LEAP). addition, results from a study compar- ed as saying, “FDA cannot identify a Compared with bosentan, ambrisen- ing anidulafungin to fluconazole in the specific patient population where we tan costs roughly the same (ie, approxi- management of invasive candidiasis believe the benefits of using Trasylol® mately $50,000 per year). Bosentan is were published, and anidulafungin was [aprotinin] outweigh the risks.” given twice a day, while ambrisentan found to be noninferior to fluconazole. The FDA’s decision not to recall is given once a day. Anidulafungin was selected for the aprotinin was intended to prevent There is limited information pub- Formulary because it results in the a shortage of alternatives (ie, amin- lished on the efficacy of ambrisentan; most potential cost savings. ocaproic acid and tranexamic acid). but there is a theoretical pharmaco- Aprotinin is a proteolytic enzyme Shands at UF has been able to get an logic advantage for ambrisentan; it is from bovine lung that has a labeled ample supply of aminocaproic acid more specific for blocking endothelin indication for the prevention of blood and tranexamic acid to be used as an A, which is responsible for vasocon- loss and transfusion in patients under- alternative. Based on the new warn- striction and tissue damage in the going surgery requiring cardiopulmo- ings and the availability of alterna- pulmonary vasculature. nary bypass. It was deleted from the tives agents, the P&T Committee Both bosentan and ambrisentan are Formulary and designated nonformu- determined that the continued use pregnancy risk category X because of lary and not available after marketing of aprotinin is not warranted at this their teratogenic potential. Both also was suspended based on recent safety